Aims: To explore possible changes in expression and/or function of alpha(1)- and beta-adrenoceptor subtypes as a cause for bladder dysfunction in a rat model of bladder outlet obstruction (BOO).
Methods: BOO was induced in rats by partial urethral ligature. Contraction and relaxation experiments were performed with isolated bladder strips from BOO, sham-operated and non-operated (control) rats 7 days after BOO induction. mRNA expression of alpha(1)- and beta-adrenoceptor subtypes was assessed by quantitative real-time PCR.
Results: Receptor-independent contraction or relaxation did not differ between BOO and sham rats. The alpha(1)-agonists methoxamine and A-61,603 caused only weak contraction without major differences between groups. Against KCl-induced tone, the beta-adrenoceptor agonists noradrenaline and isoprenaline caused similar relaxation in BOO and sham rats, whereas relaxation in response to the beta(3)-selective BRL 37,344 was attenuated. Against passive tension, noradrenaline induced relaxation in sham and control rats; in contrast, noradrenaline induced contraction at low concentrations and relaxation at high concentrations in BOO rats. The contraction component was abolished by the alpha(1)-antagonist prazosin. The mRNA expression of alpha(1D)-adrenoceptors was increased in BOO, whereas none of the other receptor mRNAs were up-regulated.
Conclusions: In a rat BOO model, weak contraction responses to alpha(1)-agonists and relaxation responses to beta-agonists are not altered to a major extent. Nevertheless, relaxation responses to the endogenous agonist noradrenaline are turned into alpha(1)-adrenoceptor-mediated contraction responses in BOO, possibly due to an up-regulation of alpha(1D)-adrenoceptors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/nau.20642 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Heightened SAM- and HPA-axis activity during acute stress impairs decision-making: A systematic review on underlying neuropharmacological mechanisms.
Neurobiol Stress
July 2024
Department of Psychiatry, University Medical Centre, Utrecht, the Netherlands.
Individuals might be exposed to intense acute stress while having to make decisions with far-reaching consequences. Acute stress impairs processes required for decision-making by activating different biological stress cascades that in turn affect the brain. By knowing which stress system, brain areas, and receptors are responsible for compromised decision-making processes, we can effectively find potential pharmaceutics that can prevent the deteriorating effects of acute stress.
View Article and Find Full Text PDFNoradrenergic tone is not required for neuronal activity-induced rebound sleep in zebrafish.
J Comp Physiol B
June 2024
Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, UK.
Sleep pressure builds during wakefulness, but the mechanisms underlying this homeostatic process are poorly understood. One zebrafish model suggests that sleep pressure increases as a function of global neuronal activity, such as during sleep deprivation or acute exposure to drugs that induce widespread brain activation. Given that the arousal-promoting noradrenergic system is important for maintaining heightened neuronal activity during wakefulness, we hypothesised that genetic and pharmacological reduction of noradrenergic tone during drug-induced neuronal activation would dampen subsequent rebound sleep in zebrafish larvae.
View Article and Find Full Text PDFAdrenoceptors in the Lower Urinary Tract.
Handb Exp Pharmacol
September 2024
Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
Adrenoceptors importantly contribute to the physiological regulation of lower urinary tract (LUT) function and have become a target of several clinically successful treatments for major LUT diseases. In the bladder dome, β-adrenoceptor subtypes are found in multiple cell types and mediate relaxation of detrusor smooth muscle, perhaps partly indirectly by acting on afferent nerves and cells of the mucosa. β-adrenoceptor agonists such as mirabegron and vibegron are used to treat overactive bladder syndrome.
View Article and Find Full Text PDFCatecholamine-dependent hyperpolarization of the junctional membrane via β2- adrenoreceptor/G-protein/α2-Na-K-ATPase pathway.
Brain Res
November 2022
Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Federal Research Center ''Kazan Scientific Center of RAS", 2/31 Lobachevsky St, box 30, Kazan, RT 420111, Russia.
We investigated the effects of catecholamines, adrenaline and noradrenaline, as well as β-adrenoceptor (AR) modulators on a resting membrane potential at the junctional and extrajunctional regions of mouse fast-twitch Levator auris longus muscle. The aim of the study was to find which AR subtypes, signaling molecules and Na,K-ATPase isoforms are involved in the hyperpolarizing action of catecholamines and whether this action could be accompanied by changes in the pump abundance on the sarcolemma. Adrenaline, noradrenaline and specific β2-AR agonist induced hyperpolarization of both junctional and extrajunctional membrane, but the underlying mechanisms were different.
View Article and Find Full Text PDFMirabegron attenuates porcine ureteral contractility via α1-adrenoceptor antagonism.
Naunyn Schmiedebergs Arch Pharmacol
July 2022
Centre for Urology Research, Faculty of Health Science & Medicine, Bond University, Robina, QLD, 4229, Australia.
The β-agonist mirabegron is thought to induce relaxation of the detrusor muscle, contributing to the improvement of overactive bladder symptoms. There has been recent interest in purposing mirabegron as a medical expulsive therapy drug to improve the passage of smaller kidney stones by relaxing the ureteral smooth muscles. The aim of this study was to determine the effects of mirabegron on the activity of the ureter.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!